Sodium Bicarbonate → HCID 71499275, compound

HRID 1482747Notes

Reaction equation

HRID 1482747 reaction equation
[OH:1][C:2]1[C:15]2[C@:14]34[CH2:16][CH2:17][N:18]([CH3:19])[C@@H:8]([C@:9]3([OH:21])[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4)[CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]([NH:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:34]=[N:35][C:36]([O:39]C)=[N:37][CH:38]=2)=[CH:29][CH:28]=1)=[O:23].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>>[OH:1][C:2]1[C:15]2[C@:14]34[CH2:16][CH2:17][N:18]([CH3:19])[C@@H:8]([C@:9]3([OH:21])[CH2:10][CH2:11][C:12](=[O:20])[CH2:13]4)[CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]([NH:24][CH2:25][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([C:33]2[CH:34]=[N:35][C:36](=[O:39])[NH:37][CH:38]=2)=[CH:31][CH:32]=1)=[O:23]

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 10176127Pyridinium chlorideHCID 86675507HCID 86675507, compound

Product 1

HCID 71499275HCID 71499275, compoundYield 31.5%

Conditions

Temperature
150 °C

Procedure

A mixture of 4,14-dihydroxy-N-{2-[4-(2-methoxypyrimidin-5-yl)phenyl]ethyl}-17-methyl-6-oxomorphinan-3-carboxamide (3) (0.5 g, 0.9 mmol) and pyridine hydrochloride (5 mL) was heated at 150° C. for 6 h. The reaction mixture was cooled, basified with saturated aqueous sodium bicarbonate and extracted with dichloromethane (3×40 mL). The aqueous phase was filtered and the collected brown solid was combined with the organic washes and evaporated to dryness. The residue was purified on silica eluting with dichloromethane/methanol (9:1) to dichloromethane/16% NH3 in methanol (9:1) to give 4,14-dihydroxy-17-methyl-6-oxo-N-{2-[4-(2-oxo-1,2-dihydropyrimidin-5-yl)phenyl]ethyl}morphinan-3-carboxamide (RDC6139) (0.15 g) as a white solid. This was dissolved in dichloromethane/methanol (3:1, 20 mL) and maleic acid (32 mg, 1 eq) added. The reaction mixture was stirred for 4 h and then the volatiles removed under vacuum at 40° C. The residue was freeze dried from water to give Compound 11 4,14-dihydroxy-17-methyl-6-oxo-N-{2-[4-(2-oxo-1,2-dihydropyrimidin-5-yl)phenyl]ethyl}morphinan-3-carboxamide maleate salt (0.17 g, 98%) as a white solid; LC/MS 529 (M+H)+; NMR(D2O): 1.15-1.21 (4H, m), 1.49-1.60 (1H, m), 1.65-1.90 (3H, m), 2.10-2.22 (1H, m), 2.29-2.41 (1H, m), 2.50-2.72 (5H, m), 2.90-3.00 (1H, m), 3.18-3.40 (3H, m), 3.45-3.60 (2H, m), 6.04 (2H, s), 6.95-7.05 (4H, m), 7.26 (1H, m), 8.11 (2H, bs).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with dichloromethane (3×40 mL)
  3. filtrationThe aqueous phase was filtered
  4. customevaporated to dryness
  5. customThe residue was purified on silica eluting with dichloromethane/methanol (9:1) to dichloromethane/16% NH3 in methanol (9:1)

Sources & evidence

ORD record
ord-d9e23d8c0f4141879b04ffa72668a9b8
Source dataset
uspto-grants-2016_08
Patent number
US09415045B2

Reaction notes

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